Astrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanisms that determine these different responses are poorly understood. Here we show that ephrin type-B receptor 1 (EphB1) is upregulated in injured motor neurons, which in turn can activate astrocytes through ephrin-B1-mediated stimulation of signal transducer and activator of transcription-3 (STAT3). Transcriptional analysis shows that EphB1 induces a protective and anti-inflammatory signature in astrocytes, partially linked to the STAT3 network. This is distinct from the response evoked by interleukin (IL)-6 that is known to induce both pro inflammatory and anti-inflammatory processes. Finally, we demonstrate that the EphB1-ephrin-B1 pathway is disrupted in human stem cell derived astrocyte and mouse models of amyotrophic lateral sclerosis (ALS). Our work identifies an early neuronal help-me signal that activates a neuroprotective astrocytic response, which fails in ALS, and therefore represents an attractive therapeutic target.
- MeSH
- amyotrofická laterální skleróza metabolismus MeSH
- antiflogistika farmakologie MeSH
- astrocyty cytologie metabolismus MeSH
- axony metabolismus MeSH
- interleukin-6 metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- motorické neurony metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nervus ischiadicus metabolismus MeSH
- neurony metabolismus MeSH
- neuroprotekce MeSH
- receptor EphB1 metabolismus MeSH
- signální transdukce MeSH
- transkripční faktor STAT3 metabolismus MeSH
- transkriptom MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika MeSH
- interleukin-6, mouse MeSH Prohlížeč
- interleukin-6 MeSH
- receptor EphB1 MeSH
- Stat3 protein, mouse MeSH Prohlížeč
- transkripční faktor STAT3 MeSH
